A problem for RNA interference methodologies has been to provide structures having long lifetimes in vivo for longer acting therapeutic agents. One challenge is to develop delivery agents that maintain the active agent in the circulation for longer periods, or in other biological environments.
Conventional approaches to the problem include incorporating modifications into the nucleotides of a siRNA or other nucleic acid agent to enhance its longevity. However, these methods must avoid a significant trade-off of activity for stability.
Another drawback of conventional methods is the limited availability of structural modifications that can be incorporated into nucleotides.
Moreover, nucleotides with structural modifications have so far provided only marginal improvement in the properties of gene silencing and RNA agents.
What is needed are structures and compositions that provide stable, long acting pharmaceutical ingredients for gene silencing and therapeutic strategies.
There is a continuing need for molecules that are active in RNA interference, as well as other modalities, with structures that provide long lifetimes in vivo for longer acting galenic agents.